CA2084531A1 - Derives antimigraines 4-pyrimidinyle et pyridinyle d'indol-3yl-alkylpiperazines - Google Patents

Derives antimigraines 4-pyrimidinyle et pyridinyle d'indol-3yl-alkylpiperazines

Info

Publication number: CA2084531A1
Authority: CA; Canada
Prior art keywords: methoxy; indol; propyl; pyrimidinyl; piperazine
Prior art date: 1991-12-19
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Abandoned

Application number

CA002084531A

Other languages

English (en)

Inventor

David W. Smith

Joseph P. Yevich

Andrew Williams

Edward H. Ruediger

Keith Dean Combrink

Bradley Clyde Pearce

Frank D. Yocca

Ronald J. Mattson

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1991-12-19

Filing date

1992-12-04

Publication date

1993-06-20

1992-12-04 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1993-06-20 Publication of CA2084531A1 publication Critical patent/CA2084531A1/fr

Status Abandoned legal-status Critical Current

Links

230000002460 anti-migrenic effect Effects 0.000 title description 8
125000004076 pyridyl group Chemical group 0.000 title description 4
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 title description 2
208000001407 Vascular Headaches Diseases 0.000 claims abstract description 14
239000000203 mixture Substances 0.000 claims description 95
150000001875 compounds Chemical class 0.000 claims description 94
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 61
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 60
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 50
238000000034 method Methods 0.000 claims description 45
-1 cyano, hydroxy Chemical group 0.000 claims description 32
125000000217 alkyl group Chemical group 0.000 claims description 29
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
208000019695 Migraine disease Diseases 0.000 claims description 26
150000003839 salts Chemical class 0.000 claims description 16
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 13
239000001257 hydrogen Substances 0.000 claims description 13
125000003545 alkoxy group Chemical group 0.000 claims description 12
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
239000002253 acid Substances 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 6
239000012453 solvate Substances 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 5
PTXVSDKCUJCCLC-UHFFFAOYSA-N 1-hydroxyindole Chemical compound C1=CC=C2N(O)C=CC2=C1 PTXVSDKCUJCCLC-UHFFFAOYSA-N 0.000 claims description 4
208000006561 Cluster Headache Diseases 0.000 claims description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
125000006125 ethylsulfonyl group Chemical group 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
IBTDQBCNOPVYCJ-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-amine Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(N)=CC=C3NC=2)CC1 IBTDQBCNOPVYCJ-UHFFFAOYSA-N 0.000 claims description 3
206010027603 Migraine headaches Diseases 0.000 claims description 3
WRZVGHXUPBWIOO-UHFFFAOYSA-N avitriptan Chemical compound C12=CC(CS(=O)(=O)NC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC WRZVGHXUPBWIOO-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
238000007910 systemic administration Methods 0.000 claims description 3
125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
RTPGEMPUQWTOTJ-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carbonitrile Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)C#N)CC1 RTPGEMPUQWTOTJ-UHFFFAOYSA-N 0.000 claims description 2
SYVBXSCDUSJDPO-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-5-nitro-1h-indole Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)[N+]([O-])=O)CC1 SYVBXSCDUSJDPO-UHFFFAOYSA-N 0.000 claims description 2
HIQHYSPKBHAPAT-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CNC(C)=O)=CC=C3NC=2)CC1 HIQHYSPKBHAPAT-UHFFFAOYSA-N 0.000 claims description 2
IADMRNYXCINVAD-UHFFFAOYSA-N n-benzyl-n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]ethanesulfonamide Chemical compound C=1C=C2NC=C(CCCN3CCN(CC3)C=3C(=CN=CN=3)OC)C2=CC=1CN(S(=O)(=O)CC)CC1=CC=CC=C1 IADMRNYXCINVAD-UHFFFAOYSA-N 0.000 claims description 2
DHFOXXSSNOLXLQ-UHFFFAOYSA-N n-butyl-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxamide Chemical compound C12=CC(C(=O)NCCCC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC DHFOXXSSNOLXLQ-UHFFFAOYSA-N 0.000 claims description 2
STTZIYOGYXNCJJ-UHFFFAOYSA-N 1,1,1-trifluoro-n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)N(C)S(=O)(=O)C(F)(F)F)CC1 STTZIYOGYXNCJJ-UHFFFAOYSA-N 0.000 claims 1
OVXCQLRRCQNGBY-UHFFFAOYSA-N 1-[3-[3-[4-(3-methoxypyridin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound C12=CC(CS(=O)(=O)NC)=CC=C2NC=C1CCCN(CC1)CCN1C1=CC=NC=C1OC OVXCQLRRCQNGBY-UHFFFAOYSA-N 0.000 claims 1
AKGZJDYNQGZZKQ-UHFFFAOYSA-N 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylmethanesulfonamide Chemical compound C12=CC(CS(=O)(=O)NC)=CC=C2NC=C1CCCN(CC1C)CCN1C1=NC=NC=C1OC AKGZJDYNQGZZKQ-UHFFFAOYSA-N 0.000 claims 1
QKBUNBGWOJHAOI-UHFFFAOYSA-N 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]-n,n-dimethylmethanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CS(=O)(=O)N(C)C)=CC=C3NC=2)CC1 QKBUNBGWOJHAOI-UHFFFAOYSA-N 0.000 claims 1
JMNJPZYYLUALFK-UHFFFAOYSA-N 1-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]ethanone Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)C(C)=O)CC1 JMNJPZYYLUALFK-UHFFFAOYSA-N 0.000 claims 1
GIEJMDKFKNPLOV-UHFFFAOYSA-N 2,2,2-trifluoro-n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(NC(=O)C(F)(F)F)=CC=C3NC=2)CC1 GIEJMDKFKNPLOV-UHFFFAOYSA-N 0.000 claims 1
HYHYARGSQDRKBV-UHFFFAOYSA-N 2-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CC(N)=O)=CC=C3NC=2)CC1 HYHYARGSQDRKBV-UHFFFAOYSA-N 0.000 claims 1
WIESNRIAUAAAKN-UHFFFAOYSA-N 2-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]oxy]acetonitrile Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(OCC#N)=CC=C3NC=2)CC1 WIESNRIAUAAAKN-UHFFFAOYSA-N 0.000 claims 1
IZKSPDDPCCFXFI-UHFFFAOYSA-N 3-[3-[4-(3-methoxypyridin-4-yl)piperazin-1-yl]propyl]-1h-indole Chemical compound COC1=CN=CC=C1N1CCN(CCCC=2C3=CC=CC=C3NC=2)CC1 IZKSPDDPCCFXFI-UHFFFAOYSA-N 0.000 claims 1
WZKOGWNTMBGKHG-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indole-5-carboxamide Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(=CC=C3NC=2)C(N)=O)CC1 WZKOGWNTMBGKHG-UHFFFAOYSA-N 0.000 claims 1
VBTUHIJWHRUHJA-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-5-(2-methylsulfonylethyl)-1h-indole Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(CCS(C)(=O)=O)=CC=C3NC=2)CC1 VBTUHIJWHRUHJA-UHFFFAOYSA-N 0.000 claims 1
GAFUZWCJMTXSDI-UHFFFAOYSA-N 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-n-methyl-1h-indole-5-carboxamide Chemical compound C12=CC(C(=O)NC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC GAFUZWCJMTXSDI-UHFFFAOYSA-N 0.000 claims 1
VPWKKLQAJWALMT-UHFFFAOYSA-N [3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CS(N)(=O)=O)=CC=C3NC=2)CC1 VPWKKLQAJWALMT-UHFFFAOYSA-N 0.000 claims 1
AVGNIAXJZABVOT-UHFFFAOYSA-N benzyl n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]carbamate Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(NC(=O)OCC=4C=CC=CC=4)=CC=C3NC=2)CC1 AVGNIAXJZABVOT-UHFFFAOYSA-N 0.000 claims 1
239000002552 dosage form Substances 0.000 claims 1
NIKWZIOCGGZIQE-UHFFFAOYSA-N ethyl 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound C12=CC(C(=O)OCC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC NIKWZIOCGGZIQE-UHFFFAOYSA-N 0.000 claims 1
GDJRVMWAHVYIST-UHFFFAOYSA-N methyl 3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxylate Chemical compound C12=CC(C(=O)OC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC GDJRVMWAHVYIST-UHFFFAOYSA-N 0.000 claims 1
ZBKOFVZDJIPULR-UHFFFAOYSA-N methyl n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]carbamate Chemical compound C12=CC(NC(=O)OC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC ZBKOFVZDJIPULR-UHFFFAOYSA-N 0.000 claims 1
KFCIVNWEXGPJDC-UHFFFAOYSA-N n-(ethylsulfonylmethyl)-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-amine Chemical compound C12=CC(NCS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC KFCIVNWEXGPJDC-UHFFFAOYSA-N 0.000 claims 1
HXDRKCWISZTWQP-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-2-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]-n-methylethanesulfonamide Chemical compound C12=CC(N(C)S(=O)(=O)CC)=CC=C2NC=C1CCCN(C(C1)C)CCN1C1=NC=NC=C1OC HXDRKCWISZTWQP-UHFFFAOYSA-N 0.000 claims 1
CBTZBEWYHRJTSX-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-2-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]ethanesulfonamide Chemical compound C12=CC(NS(=O)(=O)CC)=CC=C2NC=C1CCCN(C(C1)C)CCN1C1=NC=NC=C1OC CBTZBEWYHRJTSX-UHFFFAOYSA-N 0.000 claims 1
SGGOWYQGSMJOGP-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]ethanesulfonamide Chemical compound C12=CC(NS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1C)CCN1C1=NC=NC=C1OC SGGOWYQGSMJOGP-UHFFFAOYSA-N 0.000 claims 1
JBOOOOMNYZLORK-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(NS(C)(=O)=O)=CC=C3NC=2)CC1 JBOOOOMNYZLORK-UHFFFAOYSA-N 0.000 claims 1
WCEUGZUTYOMFFC-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(NC(C)=O)=CC=C3NC=2)CC1 WCEUGZUTYOMFFC-UHFFFAOYSA-N 0.000 claims 1
WGMBLKAFPNRDNE-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]ethanesulfonamide Chemical compound C12=CC(NS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC WGMBLKAFPNRDNE-UHFFFAOYSA-N 0.000 claims 1
JUBZHJCIFSRARM-UHFFFAOYSA-N n-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]formamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(NC=O)=CC=C3NC=2)CC1 JUBZHJCIFSRARM-UHFFFAOYSA-N 0.000 claims 1
YOWLUUHOUHAWFX-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]methyl]ethanesulfonamide Chemical compound C12=CC(CNS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1C)CCN1C1=NC=NC=C1OC YOWLUUHOUHAWFX-UHFFFAOYSA-N 0.000 claims 1
RCMNQXSWINTQDD-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)-3-methylpiperazin-1-yl]propyl]-1h-indol-5-yl]methyl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1C(C)CN(CCCC=2C3=CC(CNS(C)(=O)=O)=CC=C3NC=2)CC1 RCMNQXSWINTQDD-UHFFFAOYSA-N 0.000 claims 1
NCTRAKLBBXCNDM-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]-n-methylethanesulfonamide Chemical compound C12=CC(CN(C)S(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC NCTRAKLBBXCNDM-UHFFFAOYSA-N 0.000 claims 1
XSPLCASBMXEWCA-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]ethanesulfonamide Chemical compound C12=CC(CNS(=O)(=O)CC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC XSPLCASBMXEWCA-UHFFFAOYSA-N 0.000 claims 1
WMGLHEUAEXJDLA-UHFFFAOYSA-N n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CNS(C)(=O)=O)=CC=C3NC=2)CC1 WMGLHEUAEXJDLA-UHFFFAOYSA-N 0.000 claims 1
HWRXBDAJIPZZSU-UHFFFAOYSA-N n-benzyl-2-[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]acetamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CC(=O)NCC=4C=CC=CC=4)=CC=C3NC=2)CC1 HWRXBDAJIPZZSU-UHFFFAOYSA-N 0.000 claims 1
IMLQDCIEEBSNIV-UHFFFAOYSA-N n-benzyl-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(=CC=C3NC=2)C(=O)NCC=2C=CC=CC=2)CC1 IMLQDCIEEBSNIV-UHFFFAOYSA-N 0.000 claims 1
UPBSIWJXKOWEFO-UHFFFAOYSA-N n-benzyl-n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]methanesulfonamide Chemical compound COC1=CN=CN=C1N1CCN(CCCC=2C3=CC(CN(CC=4C=CC=CC=4)S(C)(=O)=O)=CC=C3NC=2)CC1 UPBSIWJXKOWEFO-UHFFFAOYSA-N 0.000 claims 1
DVRMBCHHTORHDP-UHFFFAOYSA-N n-ethyl-3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indole-5-carboxamide Chemical compound C12=CC(C(=O)NCC)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC DVRMBCHHTORHDP-UHFFFAOYSA-N 0.000 claims 1
DHUPYIIDQSQFKY-UHFFFAOYSA-N n-ethyl-n-[[3-[3-[4-(5-methoxypyrimidin-4-yl)piperazin-1-yl]propyl]-1h-indol-5-yl]methyl]methanesulfonamide Chemical compound C12=CC(CN(CC)S(C)(=O)=O)=CC=C2NC=C1CCCN(CC1)CCN1C1=NC=NC=C1OC DHUPYIIDQSQFKY-UHFFFAOYSA-N 0.000 claims 1
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239000000556 agonist Substances 0.000 abstract description 2
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239000003795 chemical substances by application Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 191
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
229910052943 magnesium sulfate Inorganic materials 0.000 description 24
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 23
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UHUZMAHDOFEXQY-UHFFFAOYSA-N tert-butyl-dimethyl-(5-trimethylsilylpent-4-ynoxy)silane Chemical compound CC(C)(C)[Si](C)(C)OCCCC#C[Si](C)(C)C UHUZMAHDOFEXQY-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
CIXRWXTXQKQWBW-UHFFFAOYSA-N trimethyl(pent-4-ynyl)silane Chemical compound C[Si](C)(C)CCCC#C CIXRWXTXQKQWBW-UHFFFAOYSA-N 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
UJMBCXLDXJUMFB-UHFFFAOYSA-K trisodium;5-oxo-1-(4-sulfonatophenyl)-4-[(4-sulfonatophenyl)diazenyl]-4h-pyrazole-3-carboxylate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)C1=NN(C=2C=CC(=CC=2)S([O-])(=O)=O)C(=O)C1N=NC1=CC=C(S([O-])(=O)=O)C=C1 UJMBCXLDXJUMFB-UHFFFAOYSA-K 0.000 description 1
238000001665 trituration Methods 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biomedical Technology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Indole Compounds (AREA)

CA002084531A 1991-12-19 1992-12-04 Derives antimigraines 4-pyrimidinyle et pyridinyle d'indol-3yl-alkylpiperazines Abandoned CA2084531A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date
US81066191A	1991-12-19	1991-12-19
US95959292A	1992-10-13	1992-10-13
US810,661		1992-10-13
US959,592		1992-10-13

Publications (1)

Publication Number	Publication Date
CA2084531A1 true CA2084531A1 (fr)	1993-06-20

Family

ID=27123378

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002084531A Abandoned CA2084531A1 (fr)	1991-12-19	1992-12-04	Derives antimigraines 4-pyrimidinyle et pyridinyle d'indol-3yl-alkylpiperazines

Country Status (15)

Country	Link
US (1)	US5434154A (fr)
EP (1)	EP0548813A1 (fr)
JP (1)	JPH05262762A (fr)
CN (1)	CN1085556A (fr)
AU (1)	AU661527B2 (fr)
CA (1)	CA2084531A1 (fr)
CZ (1)	CZ359292A3 (fr)
FI (1)	FI925737L (fr)
IL (1)	IL104024A (fr)
MX (1)	MX9207114A (fr)
NO (1)	NO302522B1 (fr)
NZ (1)	NZ245439A (fr)
PH (1)	PH30988A (fr)
RU (1)	RU2114111C1 (fr)
TW (1)	TW221420B (fr)

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GB9415575D0 (en) *	1994-08-02	1994-09-21	Merck Sharp & Dohme	Therapeutic agents
US5550239A (en) *	1994-11-08	1996-08-27	Bristol-Myers Squibb Company	Process for large-scale production of indolyl alkyl pyrimidinyl piperazine compounds
GB9423682D0 (en) *	1994-11-23	1995-01-11	Merck Sharp & Dohme	Therapeutic agents
WO1997011695A1 (fr) *	1995-09-28	1997-04-03	Merck Sharp & Dohme Limited	Derives d'indolylpropyl-piperazine a substitution utilises comme agonistes de 5-ht¿1d alpha?
GB9501865D0 (en) *	1995-01-31	1995-03-22	Merck Sharp & Dohme	Therapeutic agents
US5618816A (en) *	1995-03-02	1997-04-08	Bristol-Myers Squibb Company	Antimigraine 1,2,5-thiadiazole derivatives of indolylalkyl-pyridnyl and pyrimidinylpiperazines
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JPH09124643A (ja) *	1995-08-14	1997-05-13	Bristol Myers Squibb Co	抗うつ作用を有する１−アリールアルキル−４−（アルコキシピリジニル）−又は４−（アルコキシピリミジニル）ピペラジン誘導体
GB9519563D0 (en) *	1995-09-26	1995-11-29	Merck Sharp & Dohme	Therapeutic agents
AU7319096A (en) *	1995-11-02	1997-05-22	Merck Sharp & Dohme Limited	Bicyclic heteroaryl-alkylene-(homo)piperazinones and thione analogues thereof, their preparation and their use as selective agonists of 5-ht1-like receptors
GB9523250D0 (en) *	1995-11-14	1996-01-17	Merck Sharp & Dohme	Therapeutic agents
GB9609374D0 (en) *	1996-05-03	1996-07-10	Merck Sharp & Dohme	Therapeutic agents
US5811551A (en) *	1996-08-13	1998-09-22	Merck & Co., Inc.	Palladium catalyzed indolization
US5808064A (en) *	1996-08-13	1998-09-15	Merck & Co., Inc.	Palladium catalyzed indolization
US5877329A (en) *	1996-08-13	1999-03-02	Merck & Co., Inc.	Palladium catalyzed indolization
US5891885A (en) *	1996-10-09	1999-04-06	Algos Pharmaceutical Corporation	Method for treating migraine
GB9714383D0 (en) *	1997-07-08	1997-09-10	Pfizer Ltd	Improved process
DE19756036A1 (de) *	1997-12-17	1999-06-24	Merck Patent Gmbh	Amid- und Harnstoffderivate
WO2002044159A2 (fr) *	2000-11-29	2002-06-06	Eli Lilly And Company	1-(2-m-methanesulfonamidophenylethyl)-4-(m-trifluoromethylphenyl) piperazine, ses sels acceptables sur le plan pharmaceutique et ses solvants
DE10102944A1 (de) *	2001-01-23	2002-07-25	Merck Patent Gmbh	Verfahren zur Herstellung von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon und dessen Salzen
US20030017175A1 (en) *	2001-07-05	2003-01-23	R.T. Alamo Ventures I, Inc.	Sublingual administration of dihydroergotamine for the treatment of migraine
US20030198669A1 (en) *	2001-07-05	2003-10-23	R.T. Alamo Ventures I, Llc	Compositions and methods for rapid dissolving formulations of dihydroergotamine and caffeine for the treatment of migraine
US6685951B2 (en)	2001-07-05	2004-02-03	R. T. Alamo Ventures I, Inc.	Administration of dihydroergotamine as a sublingual spray or aerosol for the treatment of migraine
CA2476490C (fr) *	2002-02-13	2010-08-10	Meiji Dairies Corporation	Derives d'indole substitues avec des alcools a longue chaine et medicaments contenant ceux-ci
DE102004047517A1 (de) *	2004-09-28	2006-03-30	Merck Patent Gmbh	Neuartige Kristallform von (3-Cyan-1H-indol-7-yl)-[4-(4-fluorphenethyl)-piperazin-1-yl]-methanon, Hydrochlorid
WO2006129190A1 (fr) *	2005-06-03	2006-12-07	Glenmark Pharmaceuticals Limited	Procede de preparation de l'almotriptan
RU2461556C2 (ru) *	2006-12-30	2012-09-20	Эбботт Гмбх Унд Ко. Кг	Замещенные производные оксидола и их применение в качестве лигандов рецептора вазопрессина
PL2425820T3 (pl)	2007-02-11	2015-08-31	Map Pharmaceuticals Inc	Sposób terapeutycznego stosowania dhe w celu umożliwienia szybkiego złagodzenia migreny przy jednoczesnym zminimalizowaniu profilu działań niepożądanych
EP2036888A1 (fr) *	2007-09-17	2009-03-18	Laboratorios del Dr. Esteve S.A.	Sulfonamides à substitution naphtyl
DK2734634T3 (da)	2011-07-22	2019-10-21	Univ Chicago	Igf-1 til anvendelse til behandling af migræne
EP2935280A4 (fr)	2012-12-21	2016-05-25	Map Pharmaceuticals Inc	Composés 8'-hydroxy-dihydroergotamine et compositions associées
CN104163813B (zh) *	2013-05-16	2017-02-01	广东东阳光药业有限公司	取代的吲哚化合物及其使用方法和用途
WO2015014256A1 (fr)	2013-07-29	2015-02-05	Sunshine Lake Pharma Co., Ltd.	Composés hétéroaryle substitués et procédés d'utilisation
CN104725363B (zh) *	2013-12-20	2019-03-01	广东东阳光药业有限公司	取代的哌嗪化合物及其使用方法和用途
EP3083589B1 (fr) *	2013-12-20	2019-12-18	Sunshine Lake Pharma Co., Ltd.	Composés pipéraziniques substitués et leurs procédés d'utilisation
CN106243088B (zh) *	2015-06-03	2019-01-04	广东东阳光药业有限公司	取代的哌嗪化合物及其使用方法和用途
CN111386272B (zh) *	2017-10-27	2023-01-06	费森尤斯卡比肿瘤学有限公司	一种改进的瑞博西尼及其盐的制备方法

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GB944443A (fr) *	1959-09-25	1900-01-01
GB1189064A (en)	1967-05-01	1970-04-22	Sterling Drug Inc	Indole Derivatives
GR79215B (fr)	1982-06-07	1984-10-22	Glaxo Group Ltd
GB2162522B (en)	1984-08-01	1988-02-24	Glaxo Group Ltd	An indole derivative
US4954502A (en) *	1988-06-10	1990-09-04	Bristol-Myers Squibb Company	1-indolyalkyl-4-(substituted-pyridinyl)piperazines
FR2635104B1 (fr) *	1988-08-03	1992-04-30	Synthelabo	Derives d'indolone, leur preparation et leur application en therapeutique
GB8830312D0 (en)	1988-12-28	1989-02-22	Lundbeck & Co As H	Heterocyclic compounds
JP2871811B2 (ja)	1990-02-28	1999-03-17	サントリー株式会社	縮合７員環系化合物
CA2043709C (fr) *	1990-06-29	2002-01-22	David W. Smith	Derives pour combattre la migraine d'alcoxypirimidine
US5077293A (en) *	1990-06-29	1991-12-31	Bristol-Myers Squibb Co.	1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines

1992
- 1992-12-04 CA CA002084531A patent/CA2084531A1/fr not_active Abandoned
- 1992-12-07 CZ CS923592A patent/CZ359292A3/cs unknown
- 1992-12-08 IL IL104024A patent/IL104024A/xx not_active IP Right Cessation
- 1992-12-09 MX MX9207114A patent/MX9207114A/es unknown
- 1992-12-10 AU AU30034/92A patent/AU661527B2/en not_active Ceased
- 1992-12-10 NO NO924764A patent/NO302522B1/no unknown
- 1992-12-11 NZ NZ245439A patent/NZ245439A/xx unknown
- 1992-12-14 TW TW081110009A patent/TW221420B/zh active
- 1992-12-15 PH PH45427A patent/PH30988A/en unknown
- 1992-12-17 FI FI925737A patent/FI925737L/fi not_active Application Discontinuation
- 1992-12-17 EP EP92121519A patent/EP0548813A1/fr not_active Ceased
- 1992-12-17 RU RU92016241A patent/RU2114111C1/ru active
- 1992-12-18 JP JP4361763A patent/JPH05262762A/ja active Pending
1993
- 1993-01-02 CN CN93101186A patent/CN1085556A/zh active Pending
1994
- 1994-04-26 US US08/233,545 patent/US5434154A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
FI925737A7 (fi)	1993-06-20
FI925737L (fi)	1993-06-20
CN1085556A (zh)	1994-04-20
NZ245439A (en)	1995-07-26
PH30988A (en)	1997-12-23
MX9207114A (es)	1993-07-01
NO924764D0 (no)	1992-12-10
EP0548813A1 (fr)	1993-06-30
AU661527B2 (en)	1995-07-27
US5434154A (en)	1995-07-18
FI925737A0 (fi)	1992-12-17
RU2114111C1 (ru)	1998-06-27
NO924764L (no)	1993-06-21
TW221420B (fr)	1994-03-01
JPH05262762A (ja)	1993-10-12
AU3003492A (en)	1994-03-24
IL104024A (en)	1997-04-15
CZ359292A3 (en)	1994-01-19
NO302522B1 (no)	1998-03-16

Legal Events

Date	Code	Title	Description
1999-12-06	FZDE	Discontinued

Publication	Publication Date	Title
US5434154A (en)	1995-07-18	Antimigraine 4-pyrimidinyl and pyridinyl derivatives of indol-3yl-alkylpiperazines
US5300506A (en)	1994-04-05	Indolylalkyl derivatives of pyrimidinylpiperazine for treating vascular headache
JP2786480B2 (ja)	1998-08-13	１―インドリルアルキル―４―（置換ピリジニル）ピペラジン
US5077293A (en)	1991-12-31	1-indolyalkyl-4-(alkoxypyrimidinyl)piperazines
RU2095360C1 (ru)	1997-11-10	Производные индола, их оптические изомеры и фармацевтически приемлемые соли
US5578612A (en)	1996-11-26	Indole derivatives
AU2001246671B2 (en)	2006-03-16	Indolin-2-one derivatives, preparation and their use as ocytocin receptor ligands
JP3157179B2 (ja)	2001-04-16	３−アリールカルボニル−１−アミノアルキル−１ｈ−インドール含有抗緑内障組成物
JPH07206818A (ja)	1995-08-08	インドリルシクロアルカニルアミン抗偏頭痛剤
US5559129A (en)	1996-09-24	Indole derivatives
US5618816A (en)	1997-04-08	Antimigraine 1,2,5-thiadiazole derivatives of indolylalkyl-pyridnyl and pyrimidinylpiperazines
AU673098B2 (en)	1996-10-24	Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines
US5521188A (en)	1996-05-28	Antimigraine cyclobutenedione derivatives of indolylalkyl-pyridinyl and pyrimidinylpiperazines
JPH0741481A (ja)	1995-02-10	両性型三環系化合物